SOLUTION CONFORMATION OF HUMAN NEUROPEPTIDE-Y BY H-1 NUCLEAR-MAGNETIC-RESONANCE AND RESTRAINED MOLECULAR-DYNAMICS

被引:80
作者
DARBON, H
BERNASSAU, JM
DELEUZE, C
CHENU, J
ROUSSEL, A
CAMBILLAU, C
机构
[1] SANOFI RECH,MONTPELLIER,FRANCE
[2] SANOFI RECH,TOULOUSE,FRANCE
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1992年 / 209卷 / 02期
关键词
D O I
10.1111/j.1432-1033.1992.tb17346.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The solution structure of human neuropeptide Y has been solved by conventional two-dimensional NMR techniques followed by distance-geometry and molecular-dynamics methods. The conformation obtained is composed of two short contiguous alpha-helices comprising residues 15-26 and 28-35, linked by a hinge inducing a 100-degrees angle. The first helix (15 - 26) is connected to a polyproline stretch (residues 1 - 10) by a tight hairpin (residues 11 - 14). The helices and the polyproline stretch are packed together by hydrophobic interactions. This structure is related to that of the homologous avian pancreatic polypeptide and bovine pancreatic polypeptide. The C- and N-terminii, known to be involved in the biological activity for respectively the receptor binding and activation, are close together in space. The side chains of residues Arg33, Arg35 and Tyr36 on the one hand, and Tyr1 and Pro2 on the other, form a continuous solvent-exposed surface of 4.9 nm2 which is supposed to interact with the receptor for neuropeptide Y.
引用
收藏
页码:765 / 771
页数:7
相关论文
共 23 条
  • [1] NEUROPEPTIDE-Y DISTRIBUTION IN HUMAN-BRAIN
    ADRIAN, TE
    ALLEN, JM
    BLOOM, SR
    GHATEI, MA
    ROSSOR, MN
    ROBERTS, GW
    CROW, TJ
    TATEMOTO, K
    POLAK, JM
    [J]. NATURE, 1983, 306 (5943) : 584 - 586
  • [2] ALLEN JM, 1986, NEUROCHEM INT, V8, P1, DOI 10.1016/0197-0186(86)90093-8
  • [3] ALLEN JM, 1987, P NATL ACAD SCI USA, V84, P2432
  • [4] BECKSICKINGER AG, 1990, INT J PEPT PROT RES, V36, P522
  • [5] BENCHENKROUN MT, 1991, 12TH P AM PEPT S, P75
  • [6] X-RAY-ANALYSIS (1.4-A RESOLUTION) OF AVIAN PANCREATIC-POLYPEPTIDE - SMALL GLOBULAR PROTEIN HORMONE
    BLUNDELL, TL
    PITTS, JE
    TICKLE, IJ
    WOOD, SP
    WU, CW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (07): : 4175 - 4179
  • [7] A SERINE PROTEASE TRIAD FORMS THE CATALYTIC CENTER OF A TRIACYLGLYCEROL LIPASE
    BRADY, L
    BRZOZOWSKI, AM
    DEREWENDA, ZS
    DODSON, E
    DODSON, G
    TOLLEY, S
    TURKENBURG, JP
    CHRISTIANSEN, L
    HUGEJENSEN, B
    NORSKOV, L
    THIM, L
    MENGE, U
    [J]. NATURE, 1990, 343 (6260) : 767 - 770
  • [8] CALCULATION OF PROTEIN CONFORMATIONS BY PROTON PROTON DISTANCE CONSTRAINTS - A NEW EFFICIENT ALGORITHM
    BRAUN, W
    GO, N
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1985, 186 (03) : 611 - 626
  • [9] BRUNGER AT, 1990, X PLOR V21 MANUAL
  • [10] STRUCTURE OF NEUROPEPTIDE-Y DIMER IN SOLUTION
    COWLEY, DJ
    HOFLACK, JM
    PELTON, JT
    SAUDEK, V
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 205 (03): : 1099 - 1106